Chronobiology of the hair follicle:: Hunting the "hair cycle clock"
Chronobiology of the hair follicle:: Hunting the "hair cycle clock"
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DOI：
10.1038/sj.jidsp.5640241
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发表时间：
1999-12-01
影响因子：
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通讯作者：
Botchkarev, VA
中科院分区：
文献类型：
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作者：
Paus, R;Müller-Röver, S;Botchkarev, VA
毛囊(HF)是唯一的哺乳动物器官，经历了从长生长阶段(生长期)到快速的、由细胞凋亡驱动的器官退化(退化期)到相对“休止期”(终止期)的生命周期的转变。这些转换背后的控制显然驻留在HF本身和/或周围，并可能反映-本质上自主的，但高度可操作的-局部信号环境的变化，例如，头发生长调节生长因子、细胞因子、激素和黏附分子。然而，在局部信号环境中驱动这些循环开关的“毛发周期时钟”(CC)的分子性质和组织仍然不清楚，甚至还没有一个完全令人满意的毛发周期控制理论。由于破译肝癌具有极其重要的临床意义，而且迫切需要相应的工作假说来指导设计更深入的实验，以确定肝癌背后难以捉摸的中央“振荡器”机制，我们讨论了任何令人信服的肝癌理论应满足的基本要求，在论证了至少四种不同的计时装置构成HP时间生物学(“形态发生钟”、“周期诱导器”、“去同步化”和实际的肝癌)之后，对以前提出的肝癌理论进行了简要和批判性的回顾。鉴于肝细胞癌和细胞周期机制之间有趣的调控相似性，我们在这里提出，肝细胞癌可能是由自主性的、细胞周期耦合的HF间充质分泌活动驱动的，即通过真皮乳头成纤维细胞G0/G1相关的“乳头形态原”分泌的变化。希望这一具有挑衅性的假设将鼓励提出新的、全面的肝细胞癌理论。
The hair follicle (HF) is the only mammalian organ that undergoes life-long, cyclic transformations from long stages of growth (anagen), via rapid, apoptosis-driven organ involution (catagen) to a stage of relative "resting" (telogen). The controls that underlie these transformations clearly reside in and/or around the HF itself, and are likely to reflect - essentially autonomous, yet highly manipulable - changes in the local signalling milieu of e.g., hair growth-modulatory growth factors, cytokines, hormones and adhesion molecules. Yet the molecular nature and organization of the "hair cycle clock" (HCC) that drives these cyclic switches in the local signalling milieu remain obscure, and there is not even a fully satisfactory theory of hair cycle control. Since deciphering of the HCC is of paramount clinical importance, and since corresponding working hypotheses are badly needed to guide the design of more incisive experiments that identify the elusive central "oscillator" mechanism behind the HCC, we discuss basic requirements any convincing HCC theory should meet, After arguing that at least four distinct timing devices underlie HP chronobiology ("morphogenesis clock", "cycling inducer", "desynchronizer", and the actual HCC), previously proposed HCC theories are briefly and critically reviewed. In the light of intriguing regulatory similarities between the HCC and the cell cycle machinery, we suggest here that the HCC may be driven by autonomous, cell cycle-coupled secretory activities of the HF mesenchyme, namely by changes in the G0/G1-associated secretion of "papilla morphogens" by dermal papilla fibroblasts. Hopefully, this provocative hypothesis will encourage the proposition of novel, comprehensive HCC theories.